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Chapter 16

Schizophrenia

http://www.npr.org/programs/atc/features/2002/aug/schizophrenia/

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Schizophrenia

A serious mental disorder characterized by disordered thoughts, delusions, hallucinations, and mood disturbance.

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Schizophrenia

Positive SymptomsDelusionsHallucinationsDisorganized behavior

Negative SymptomsSocial withdrawalMood disturbanceReduced motivation

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Schizophrenia May Have Several Outcomes

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Genetics and Schizophrenia Concordance rate in identical twins is 50%. Adoption studies support a strong genetic role. As many as 70 genes may be involved.

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A Possible Genetic MarkerA majority of patients and 45% of their relatives show abnormal intrusions of saccades in smooth pursuit tasks.

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Treatment of Schizophrenia

No effective treatments prior to about 1950 Discovery of chlorpromazine (Thorazine)

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SchizophreniaPositive symptoms

Dopamine hypothesis:Overactivity of dopamine in

mesolimbic pathway (VTA to nucleus accumbens and amygdala)

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SchizophreniaHow are positive symptoms related to

dopamine?

Hypothesis: Mesolimbic system important for reinforcement of behavior We all have irrational thoughts, but usually brush them aside But if mesolimbic system was active when the thought

occurred, we might take it more seriously, leading to delusions

Confirming piece of evidence: schizophrenics often report euphoria at onset of positive symptoms

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Hypothesis cont.: Disordered thinking?

System so active that it does not discriminate between thoughts, making it hard to follow a logical sequence

Terrifying element of delusions?Strong dopaminergic projection to amygdala

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Dopamine HypothesisEvidence for excessive dopamine

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Dopamine and Schizophrenia Dopamine agonists

(cocaine, amphetamine) produce symptoms of psychosis.

Dopamine antagonists reduce psychotic behavior.

Patients may have abnormalities involving dopamine autoreceptors.

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SchizophreniaPositive Symptoms

Chlorpromazine: A “typical neuroleptic” A dopamine receptor blocker for D2 receptors

Clozapine: An “atypical neuroleptic” An antipsychotic drug that blocks D4 receptors

in the nucleus accumbens

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Long-term Use of Typical Neuroleptics Often Produce Serious Side Effects

Tardive dyskinesia involves tremors and involuntary movements.

Supersensitivity: increased sensitivity of neurotransmitter receptors (D2) to dopamine

Due to side effects, about 50% now use atypical neuroleptics like clozapine.

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Dopamine HypothesisEvidence for increase in D3 receptors

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Problems With a Excessive Dopamine Hypothesis 25% of patients do not respond to dopamine

antagonists. Atypical antipsychotic medications (clozapine) act

primarily on neurotransmitters other than dopamine.

Drugs change dopamine activity immediately, but patient may not improve for weeks.

PCP produces symptoms similar to schizophrenia by blocking the NMDA glutamate receptor.

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SchizophreniaNegative symptoms

Brain damage:Many of the negative symptoms are

also seen in people with brain damage

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Search for Brain AbnormalitiesEvidence for changes in ventricular size

Courtesy D.R. Weinberger, NIMH, St. Elizabeth’s Hospital, Washington, D.C.

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Schizophrenia and the Hippocampus

Cell bodies in a control participant are arranged neatly.

Cell bodies in a participant diagnosed with schizophrenia appear relatively disorganized.

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Search for Brain AbnormalitiesLoss of gray matter with age

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Search for Brain AbnormalitiesLoss of gray matter with age

Cause of delay of onset??

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The Hypofrontality Hypothesis Lower frontal lobe

activity may account for the negative symptoms of schizophrenia.

During rest (top) and an effortful cognitive test (bottom), patients with schizophrenia show less frontal lobe activity.

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How are positive & negative symptoms related?

VTA

PrefrontalCortex

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DopamineHypoactivity(too little DA)

GABA neurons

Dopamine hyperactivity(too much DA)

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Possible Causes of Brain AbnormalitiesSeasonal Effect

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Possible Causes of Brain AbnormalitiesSeasonal Effect – Flu in 2nd trimester

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Possible Causes of the Brain Abnormalities

Latitude effect: The increased incidence of schizophrenia in

people born far from the equator.Nutritional deficiency

Hunger Winter studyThiamine deficiencyVitamin D deficiency (latitude effect?)

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Possible Causes of the Brain Abnormalities

Father’s AgeLate 20s 1:121 people schizophrenic50s 1:47 people schizophrenic

Why?Maybe problem with spermatocytes

Produce sperm Must replicate every 16 days Possible copying errors

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Possible Causes of the Brain Abnormalities

Rh incompatibility Mother Rh neg, 1st baby Rh pos, 2nd baby Rh pos (antibodies attack)

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Schizophrenia

Early warning signs for children with abnormal prenatal development]\:

Children who developed schizophrenia displayed more negative affect in their facial expression and were more likely to show abnormal movements.

Children who developed schizophrenia also displayed poor social adjustment and did more poorly in school than their peers.